EFFECTS OBSERVED IN THE WHOLE ANIMAL 715 



toxicity. Rossing (1941) found a picture in acute arsenic poisoning of dam- 

 age to the reticuloendothelial system, necrosis of the hepatic cells, and 

 various degrees of acute yellow atrophy; in chronic poisoning there is fatty 

 infiltration simultaneous with progressive necrosis and congestion of the 

 bile ducts. Portal cirrhosis and ascites have been attributed to the prolonged 

 use of Fowler's solution (Franklin et al., 1950), but the etiological responsi- 

 bility of arsenic here is uncertain. Intensive intravenous arsenotherapy 

 in patients has been reported to cause damage to the liver, and certainly 

 large doses of arsphenamine in rabbits can induce a marked necrosis with 

 fatty degeneration, but the question has arisen as to whether the syphilitic 

 infection is the cause. Indeed, Thomas and Olansky (1946) stated that 

 in intensive 5-day arsenotherapy no evidence of damage to the liver could 

 be obtained and, in fact, some improvement was often noted, indicating 

 the presence of syphilitic hepatitis. Lewisite causes striking changes in the 

 liver within a few hours in most species, the sequence of events being briefly: 

 edema and congestion, distention of bile ducts, necrosis of gall bladder 

 mucosa, desquamation of epithelium, mitochondrial disintegration — by 

 4-6 hr there is cloudy swelling and biliary hemorrhages and by 12 hr the 

 liver is mottled and necrotic, the cells vacuolated, and the nuclei pycnotic 

 (Cameron et al., 1946). It was thought by Foulerton (1921) that certain 

 arsenicals have a special affinity for lipids, are carried to the liver in the 

 circulating fat, and disrupt lipid metabolism in the liver, but it seems 

 unlikely that a unique mechanism must be postulated. Whatever the ulti- 

 mate origin of the hepatic damage, these effects on the liver must contribute 

 to the observed changes in blood composition. 



Toxicology of the Organic Arsonic Acids 



The relatively low toxicity of the pentavalent arsenicals, such as atoxyl, 

 tryparsamide, and carbarsone, indicates that these compounds are not 

 immediately and quantitatively reduced to their corresponding arsenoxides, 

 and casts some doubt on the generally accepted theory that these penta- 

 valent arsenicals produce all their effects following reduction. It is known 

 that a farily large fraction of the administered pentavalent arsenical is 

 fairly rapidly excreted as such. It is probable that the penetration and 

 distribution of the tri- and pentavalent arsenicals in the tissues are quite 

 different, which complicates an interpretation of their actions based solely 

 on metabolic inhibition. Arsonic acids very seldom cause the typical reac- 

 tions seen with the trivalent arsenicals, even during chronic administration; 

 e. g., with tryparsamide and carbarsone, the occurrence of liver damage, 

 renal disturbances, dermatitis, or diarrhea is rare, and usually no indication 

 of definite vascular effects is found. This is all the more surprising when 

 one considers the relative toxic doses of the tri- and pentavalent arsenicals. 

 For example, the ratio of the maximal tolerated doses of tryparsamide and 



